Abstract ? Project 4 ? Gene Expression Project Twin research has shown that aggregate genetic effects on health are systematically modified by factors such as socioeconomic status (SES) and social relationships. In this new MIDUS project, we will begin identifying the specific pathways that integrate the effects of genes and psychosocial environments to jointly influence targeted biological risk factors for aging-related diseases. Specifically, we aim to harness new methods for genome-wide transcriptional profiling and related bioinformatic interpretive strategies to study how the expression profiles of genes central to the body's immune-inflammatory response are affected by socioeconomic standing and social relational experience. Preliminary studies show how adverse psychosocial conditions such as low SES and social isolation affect the expression of several specific sets of genes relevant to health outcomes. These studies have identified a ?Conserved Transcriptional Response to Adversity? (CTRA) marked by up-regulation of pro- inflammatory genes and down-regulation of genes involved in Type I interferon responses and production of specific antibody isotypes. Although provocative, this research has yet to be conducted in nationally representative samples and needs to be expanded to a broader range of potentially relevant psychosocial risk factors. Of particular importance is the need to examine whether psychosocial advantages might ameliorate the impact of adverse life experience. The overarching aim of this new project is to integrate gene expression profiling and related bioinformatic assessment of CTRA transcriptome profiles into the rich knowledge of psychosocial aging afforded by MIDUS. The specific aims are the following: (1) Obtain genome-wide transcriptional profiles of peripheral blood mononuclear cells (PBMCs) for participants in the MIDUS Biomarker Project; (2) Examine how cumulative socioeconomic and social relational profiles impact gene expression in this group of participants; (3) Determine if psychosocial advantage or disadvantage directly impacts gene expression, net of genetic endowment, by conducting an identical co-twin control study within this group.